Reprogramming of human fibroblasts into multipotent cells with a single ECM proteoglycan, fibromodulin

Zheng, Zhong; Jia, Jian; Zhang, Xinli; Zara, Janette N.; Yin, Wei; Chiang, Michael; Liu, Yi; Wang, Joyce; Pang, Shanchen; Ting, Kang; Soo, Chia

doi:10.1016/j.biomaterials.2012.04.049

Cited by 59 publications

(111 citation statements)

References 78 publications

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“…36,37 This finding, coupled with those from our current study, support the growing consensus that FM (and other small leucine-rich proteoglycans) has pleiotropic functions regulating intracellular signaling, cell fate determination, and stem cell niches 36e40 that extend far beyond its initially described roles in collagen assembly, organization, and degradation for extracellular matrix structural support. 18,41e43 In conclusion, the findings from our study suggest that FM alone is sufficient to restore scarless fetal repair to late-gestation animals, which normally heal with Figure 3 Fibromodulin (Fm) reduces transforming growth factor (Tgf)-b1 expression in embryonic day 18.5 (E18) fetal rat wounds.…”

Section: Discussionsupporting

confidence: 84%

Fibromodulin Is Essential for Fetal-Type Scarless Cutaneous Wound Healing

Zheng

Zhang

Dang

et al. 2016

The American Journal of Pathology

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In contrast to adult and late-gestation fetal skin wounds, which heal with scar, early-gestation fetal skin wounds display a remarkable capacity to heal scarlessly. Although the underlying mechanism of this transition from fetal-type scarless healing to adult-type healing with scar has been actively investigated for decades, in utero restoration of scarless healing in late-gestation fetal wounds has not been reported. In this study, using loss-and gain-of-function rodent fetal wound models, we identified that fibromodulin (Fm) is essential for fetal-type scarless wound healing. In particular, we found that loss of Fm can eliminate the ability of early-gestation fetal rodents to heal without scar. Meanwhile, administration of fibromodulin protein (FM) alone was capable of restoring scarless healing in lategestation rat fetal wounds, which naturally heal with scar, as characterized by dermal appendage restoration and organized collagen architectures that were virtually indistinguishable from those in age-matched unwounded skin. High Fm levels correlated with decreased transforming growth factor (TGF)-b1 expression and scarless repair, while low Fm levels correlated with increased TGF-b1 expression and scar formation. This study represents the first successful in utero attempt to induce scarless repair in late-gestation fetal wounds by using a single protein, Fm, and highlights the crucial role that the FMeTGF-b1 nexus plays in fetal-type scarless skin repair. (Am J Pathol 2016 http://dx

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Section: Discussionsupporting

confidence: 84%

Fibromodulin Is Essential for Fetal-Type Scarless Cutaneous Wound Healing

Zheng

Zhang

Dang

et al. 2016

The American Journal of Pathology

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“…Color images available online at www.liebertpub.com/tea noncollagenous proteins, including fibronectin, fibromodulin, biglycan, and decorin, all of which are known to regulate MSC activities, such as adhesion, proliferation, stemness, and differentiation. 21,[43][44][45] In addition, a variety of growth factors, such as TGF-b, IGF-1, vascular endothelial growth factor (VEGF), and connective tissue growth factor (CTGF), were found embedded in the decellularized tECM. 46 How these bioactive molecules, along with other yet-to-be-identified components in the tECM, contribute to the bioactivity of the tECM in our results remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

Tendon-Derived Extracellular Matrix Enhances Transforming Growth Factor-β3-Induced Tenogenic Differentiation of Human Adipose-Derived Stem Cells

Yang

Rothrauff

Lin

et al. 2017

Tissue Engineering Part A

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Because of the limited and unsatisfactory outcomes of clinical tendon repair, tissue engineering approaches using adult mesenchymal stem cells are being considered a promising alternative strategy to heal tendon injuries. Successful and functional tendon tissue engineering depends on harnessing the biochemical cues presented by the native tendon extracellular matrix (ECM) and the embedded tissue-specific biofactors. In this study, we have prepared and characterized the biological activities of a soluble extract of decellularized tendon ECM (tECM) on adult adipose-derived stem cells (ASCs), on the basis of histological, biochemical, and gene expression analyses. The results showed that tECM enhances the proliferation and transforming growth factor (TGF)-b3-induced tenogenesis of ASCs in both plate and scaffold cultures in vitro, and modulates matrix deposition of ASCs seeded in scaffolds. These findings suggest that combining tendon ECM extract with TGFb3 treatment is a possible alternative approach to induce tenogenesis for ASCs.

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“…Several researchers have reported that, in addition to ESC extracts, other cell extracts such as fish oocyte extracts 57 or a single extracellular matrix proteoglycan of fibromodulin 58 can promote the reprogramming of human fibroblast cells into human piPSCs or induced multipotent stem cells. In most cases, the specific proteins from the extracts that drive reprogramming are unknown.…”

Section: Pscs Reprogramming With Proteins (Pipscs)mentioning

confidence: 99%

“…Currently, to our knowledge, hiPSC generation solely based on chemically defined small molecules has not yet been reported, although hiPSCs have been generated using cell extracts and/or proteins without the use of TFs. 18,58,90 CONCLUSIONS AND PERSPECTIVES Introduction of small and large molecules can target signaling transduction pathways and can affect DNA replication, cell differentiation, apoptosis, and the reprogramming of the cells into iPSCs. Several specific small molecules can successfully enhance the reprogramming efficiencies of mouse and human somatic cells into iPSCs.…”

Section: Small Molecules Can Induce Human Ipscs In Combination With Amentioning

confidence: 99%

Generation of pluripotent stem cells without the use of genetic material

Higuchi

Ling

Kumar

et al. 2015

Laboratory Investigation

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Induced pluripotent stem cells (iPSCs) provide a platform to obtain patient-specific cells for use as a cell source in regenerative medicine. Although iPSCs do not have the ethical concerns of embryonic stem cells, iPSCs have not been widely used in clinical applications, as they are generated by gene transduction. Recently, iPSCs have been generated without the use of genetic material. For example, protein-induced PSCs and chemically induced PSCs have been generated by the use of small and large (protein) molecules. Several epigenetic characteristics are important for cell differentiation; therefore, several small-molecule inhibitors of epigenetic-modifying enzymes, such as DNA methyltransferases, histone deacetylases, histone methyltransferases, and histone demethylases, are potential candidates for the reprogramming of somatic cells into iPSCs. In this review, we discuss what types of small chemical or large (protein) molecules could be used to replace the viral transduction of genes and/or genetic reprogramming to obtain human iPSCs.

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Reprogramming of human fibroblasts into multipotent cells with a single ECM proteoglycan, fibromodulin

Cited by 59 publications

References 78 publications

Fibromodulin Is Essential for Fetal-Type Scarless Cutaneous Wound Healing

Fibromodulin Is Essential for Fetal-Type Scarless Cutaneous Wound Healing

Tendon-Derived Extracellular Matrix Enhances Transforming Growth Factor-β3-Induced Tenogenic Differentiation of Human Adipose-Derived Stem Cells

Generation of pluripotent stem cells without the use of genetic material

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